| First Author | Philp AR | Year | 2022 |
| Journal | Physiol Genomics | Volume | 54 |
| Issue | 7 | Pages | 273-282 |
| PubMed ID | 35658672 | Mgi Jnum | J:345700 |
| Mgi Id | MGI:7593818 | Doi | 10.1152/physiolgenomics.00134.2021 |
| Citation | Philp AR, et al. (2022) KCa3.1 differentially regulates trachea and bronchi epithelial gene expression in a chronic-asthma mouse model. Physiol Genomics 54(7):273-282 |
| abstractText | Ion channels are potentially exploitable as pharmacological targets to treat asthma. This study evaluated the role of KCa3.1 channels, encoded by Kcnn4, in regulating the gene expression of mouse airway epithelium and the development of asthma traits. We used the ovalbumin (OVA) challenge as an asthma model in wild-type and Kcnn4(-/-) mice, performed histological analysis, and measured serum IgE to evaluate asthma traits. We analyzed gene expression of isolated epithelial cells of trachea or bronchi using mRNA sequencing and gene ontology and performed Ussing chamber experiments in mouse trachea to evaluate anion secretion. Gene expression of epithelial cells from mouse airways differed between trachea and bronchi, indicating regional differences in the inflammatory and transepithelial transport properties of proximal and distal airways. We found that Kcnn4 silencing reduced mast cell numbers, mucus, and collagen in the airways, and reduced the amount of epithelial anion secretion in the OVA-challenged animals. In addition, gene expression was differentially modified in the trachea and bronchi, with Kcnn4 genetic silencing significantly altering the expression of genes involved in the TNF pathway, supporting the potential of KCa3.1 as a therapeutic target for asthma. |
